Search

In addition to the core symptoms defining ADHD, affected children often experience motor problems; in particular, graphomotor movements including handwriting are affected. However, in clinical settings, there is little emphasis on standardized and objective diagnosing and treatment of those difficulties. The present study investigated for the first time the effects of methylphenidate as well as physiotherapeutic treatment on objectively assessed graphomotor movements compared to a control condition, i.e. parental psychoeducation, in 58 children (mean age: 9.52 ± 1.91 years) newly diagnosed with ADHD in an outpatient clinic for child and adolescent psychiatry. Families were invited to join one of the treatment groups. Before and after 8 weeks of treatment, children performed six different tasks on a digitizing tablet which allowed the objective analysis of three important kinematic parameters of graphomotor movements (fluency, velocity, and pen pressure) in different levels of visual control and automation. Graphomotor movement fluency and velocity improves over time across the groups, especially in tasks with eyes closed. We did not find clear evidence for beneficial effects of methylphenidate or physiotherapeutic treatment on children's overall graphomotor movements suggesting that treatments need to be better tailored towards specific and individual deficits in graphomotor movements., (© 2023. The Author(s).)

Objective: In attention deficit/hyperactivity disorder (ADHD), impaired response inhibition is frequently observed. A promising non-pharmacological treatment is electroencephalography (EEG)-neurofeedback (NF) training. However, the widely used theta-down/beta-up regulation (↓θ↑β) NF protocol may not be optimal for targeting these deficits. We examined how neurofeedback protocols training the upregulation of theta and/or beta power affect inhibitory control in children and adolescents with ADHD., Methods: 64 patients with ADHD took part in the three NF trainings. Aside from parent-reported ADHD symptoms and behavioural performance data, neurophysiological parameters collected via a Go/Nogo task and corrected to account for intraindividual variability were compared in a pre-post design and to an ADHD (n = 20) as well as a typically developing control group (n = 24)., Results: The examined NF protocols resulted in similar improvements in response inhibition with the neurophysiological mechanisms differing substantially. The upregulation of theta led to a specific Nogo-P3 increase, while training beta upregulation as well as the combined protocol resulted in less specific effects., Conclusions: This study shows distinct effects of different theta/beta-neurofeedback protocols on the neural mechanisms underlying improvements in response inhibition in patients with ADHD., Significance: These effects shed further light on the oscillatory dynamics underlying cognitive control in ADHD and how these may be targeted in neurofeedback treatments., Competing Interests: Submission declaration The authors confirm that work described has not been published previously, is not currently being considered for publication elsewhere, that its publication is approved by all authors and that, if accepted, it will not be published elsewhere without the written permission of the copyright holder., (Copyright © 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

We aimed to identify promising novel medications for child and adolescent mental health problems. We systematically searched https://clinicaltrials.gov/ and https://www.clinicaltrialsregister.eu/ (from 01/01/2010-08/23/2022) for phase 2 or 3 randomized controlled trials (RCTs) of medications without regulatory approval in the US, Europe or Asia, including also RCTs of dietary interventions/probiotics. Additionally, we searched phase 4 RCTs of agents targeting unlicensed indications for children/adolescents with mental health disorders. We retrieved 234 ongoing or completed RCTs, including 26 (11%) with positive findings on ≥ 1 primary outcome, 43 (18%) with negative/unavailable results on every primary outcome, and 165 (70%) without publicly available statistical results. The only two compounds with evidence of significant effects that were replicated in ≥ 1 additional RCT without any negative RCTs were dasotraline for attention-deficit/hyperactivity disorder, and carbetocin for hyperphagia in Prader-Willi syndrome. Among other strategies, targeting specific symptom dimensions in samples stratified based on clinical characteristics or established biomarkers may increase chances of success in future development programmes., Competing Interests: Conflict of interest S Cortese declares honoraria and reimbursement for travel and accommodation expenses for lectures from the following non-profit associations: Association for Child and Adolescent Central Health (ACAMH), Canadian ADHD Alliance Resource (CADDRA), British Association of Pharmacology (BAP), and from Healthcare Convention for educational activity on ADHD. M Højlund has been a consultant to or has received honoraria from the Lundbeck Foundation, H. Lundbeck, and Otsuka. C Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Biogen, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Medscape, Menarini, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. I Baeza has received honoraria and travel support from Angelini, Otsuka-Lundbeck and Janssen. T Banaschewski served in an advisory or consultancy role for eye level, Infectopharm, Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Roche, and Takeda. He received conference support or speaker’s fee by Janssen, Medice and Takeda. He received royalities from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press; the present work is unrelated to these relationships. JK Buitelaar has been a consultant to / member of advisory board of / and/or speaker for Takeda, Medice, Angelini, Janssen, Boehringer-Ingelheim and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. D Coghill served in an advisory or consultancy role for Medice, Novartis, Servier, and Shire/Takeda. He received conference support or speaker’s fee from Medice, Servier, and Shire/Takeda. He received royalties from Cambridge University Press and Oxford University Press; He is not an employee of any of these companies, and not a stock shareholder of any of these companies and the present work is unrelated to these relationships. D Cohen has been a consultant or has received honoraria from Janssen/J&J and Otsuka; he served on a Data Safety Monitoring Board for Lundbeck. CU Correll has been a consultant and/or advisor to or has received honoraria from: AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris. He provided expert testimony for Janssen and Otsuka. He served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva. He has received grant support from Janssen and Takeda. He received royalties from UpToDate and is also a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic. E Grunblatt received grant support from MEDICE Arzneimittel Pütter GmbH & Co KG. C Moreno has received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Esteve, Exeltis, Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. M Parellada has been a consultant to or has received honoraria or grants from Angelini, Janssen Cilag, Exeltis, Lundbeck, Otsuka, Pfizer, Roche, Sage, Servier. A.M. Persico has been a consultant to and/or speaker for and has received honoraria from Servier, Sanofi, and Healx Limited. In the last 3 years, D. Purper-Ouakil reports honoraria/non-financial support from Medice and Shire/Takeda, non-financial support from HAC Pharma, and has worked as an unpaid scientific coordinator for Mensia, all outside the submitted work. In the last 2 years, B Vitiello was a paid consultant for Medice, Menarini, Angelini, and Alkermes Pharmaceuticals. ICKW reports research funding outside the submitted work from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, Takeda, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the Hong Kong Innovation and Technology Commission, the NIHR, the European Commission, and the Australian National Health and Medical Research Council, and has also received expert testimony payment from the Hong Kong Court of Final Appeal in the previous 3 years and consultancy fee from IQVIA and World Health Organization. In the last 3 years, V Roessner received no honoraria from pharmaceutical companies. He received royalties from Hogrefe, Oxford University Press; the present work is unrelated to these relationships. The other authors have no conflicts of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD], and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders., (© 2023. The Author(s).)

Introduction: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share overlapping symptomatology, particularly with regard to social impairments (including peer relationship difficulties), and they frequently co-occur. However, the nature of their co-occurrence remains unclear. Therefore, the current study aimed to examine the nature of the transdiagnostic link between ASD and ADHD from a symptomatological point of view measured with the Autism Diagnostic Observation Schedule (ADOS Module 3) and the Autism Diagnostic Interview-Revised (ADI-R)., Methods: We analyzed the social and nonsocial ASD symptom domain scores from both diagnostic instruments in 4 clinically referred groups (i.e., ASD, ADHD, ASD + ADHD, and no psychiatric diagnosis) without other co-occurring mental disorders using a two-by-two full-factorial MANOVA design with the factors ASD (yes/no) and ADHD (yes/no)., Results: We found no ASD by ADHD interaction effects across all symptom domain scores of ADOS and ADI-R, except for ADOS imagination/creativity. There were only main effects of the factor ASD but no main effects of ADHD. Follow-up contrasts showed that exclusively, ASD had an impact on the measured symptomatology in case of co-occurring ASD + ADHD., Conclusion: Overall, the results support an additive model of the symptomatology across areas of communication, social interaction, and stereotyped behaviors and restricted interests in case of the co-occurrence of ASD and ADHD when assessed with ADOS/ADI-R. Thus, one can assume that the phenotypic overlap of ASD + ADHD may be less complicated than suspected - at least with regard to ASD symptomatology - and that in the presence of ADHD, ASD symptomatology is generally well measurable with best-practice diagnostic instruments., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are two frequently co-occurring neurodevelopmental conditions that share certain symptomatology, including social difficulties. This presents practitioners with challenging (differential) diagnostic considerations, particularly in clinically more complex cases with co-occurring ASD and ADHD. Therefore, the primary aim of the current study was to apply a data-driven machine learning approach (support vector machine) to determine whether and which items from the best-practice clinical instruments for diagnosing ASD (ADOS, ADI-R) would best differentiate between four groups of individuals referred to specialized ASD clinics (i.e., ASD, ADHD, ASD + ADHD, ND = no diagnosis). We found that a subset of five features from both ADOS (clinical observation) and ADI-R (parental interview) reliably differentiated between ASD groups (ASD & ASD + ADHD) and non-ASD groups (ADHD & ND), and these features corresponded to the social-communication but also restrictive and repetitive behavior domains. In conclusion, the results of the current study support the idea that detecting ASD in individuals with suspected signs of the diagnosis, including those with co-occurring ADHD, is possible with considerably fewer items relative to the original ADOS/2 and ADI-R algorithms (i.e., 92% item reduction) while preserving relatively high diagnostic accuracy. Clinical implications and study limitations are discussed., (© 2022. The Author(s).)

Obsessive-compulsive disorder (OCD) and attention-deficit hyperactivity disorder (ADHD) are multi-faceted neuropsychiatric conditions that in many aspects appear to be each other's antipodes. We suggest a dimensional approach, according to which these partially opposing disorders fall onto a continuum that reflects variability regarding alterations of cortico-striato-thalamo-cortical (CSTC) circuits and of the processing of neural noise during cognition. By using theoretical accounts of human cognitive metacontrol, we develop a framework according to which OCD can be characterized by a chronic bias towards exaggerated cognitive persistence, equivalent to a high signal-to-noise ratio (SNR)-which facilitates perseverative behaviour but impairs mental flexibility. In contrast, ADHD is characterized by a chronic bias towards inflated cognitive flexibility, equivalent to a low SNR-which increases behavioural variability but impairs the focusing on one goal and on relevant information. We argue that, when pharmacology is not feasible, novel treatments of these disorders may involve methods to manipulate the signal-to-noise ratio via non-invasive brain stimulation techniques, in order to normalize the situational imbalance between cognitive persistence and cognitive flexibility., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In 2011, the European Society for the Study of Tourette Syndrome (ESSTS) published the first European guidelines for Tourette Syndrome (TS). We now present an update of the part on pharmacological treatment, based on a review of new literature with special attention to other evidence-based guidelines, meta-analyses, and randomized double-blinded studies. Moreover, our revision took into consideration results of a recent survey on treatment preferences conducted among ESSTS experts. The first preference should be given to psychoeducation and to behavioral approaches, as it strengthens the patients' self-regulatory control and thus his/her autonomy. Because behavioral approaches are not effective, available, or feasible in all patients, in a substantial number of patients pharmacological treatment is indicated, alone or in combination with behavioral therapy. The largest amount of evidence supports the use of dopamine blocking agents, preferably aripiprazole because of a more favorable profile of adverse events than first- and second-generation antipsychotics. Other agents that can be considered include tiapride, risperidone, and especially in case of co-existing attention deficit hyperactivity disorder (ADHD), clonidine and guanfacine. This view is supported by the results of our survey on medication preference among members of ESSTS, in which aripiprazole was indicated as the drug of first choice both in children and adults. In treatment resistant cases, treatment with agents with either a limited evidence base or risk of extrapyramidal adverse effects might be considered, including pimozide, haloperidol, topiramate, cannabis-based agents, and botulinum toxin injections. Overall, treatment of TS should be individualized, and decisions based on the patient's needs and preferences, presence of co-existing conditions, latest scientific findings as well as on the physician's preferences, experience, and local regulatory requirements., (© 2021. The Author(s).)

Tourette syndrome (TS) is a neuropsychiatric disorder with involvement of genetic and environmental factors. We investigated genetic loci previously implicated in Tourette syndrome and associated disorders in interaction with pre- and perinatal adversity in relation to tic severity using a case-only (N = 518) design. We assessed 98 single-nucleotide polymorphisms (SNPs) selected from (I) top SNPs from genome-wide association studies (GWASs) of TS; (II) top SNPs from GWASs of obsessive-compulsive disorder (OCD), attention-deficit/hyperactivity disorder (ADHD), and autism spectrum disorder (ASD); (III) SNPs previously implicated in candidate-gene studies of TS; (IV) SNPs previously implicated in OCD or ASD; and (V) tagging SNPs in neurotransmitter-related candidate genes. Linear regression models were used to examine the main effects of the SNPs on tic severity, and the interaction effect of these SNPs with a cumulative pre- and perinatal adversity score. Replication was sought for SNPs that met the threshold of significance (after correcting for multiple testing) in a replication sample (N = 678). One SNP (rs7123010), previously implicated in a TS meta-analysis, was significantly related to higher tic severity. We found a gene-environment interaction for rs6539267, another top TS GWAS SNP. These findings were not independently replicated. Our study highlights the future potential of TS GWAS top hits in gene-environment studies., (© 2021. The Author(s).)

Patients with attention deficit/(hyperactivity) disorder (AD(H)D) show increased intra-individual variability (IIV) in behavioral performance. This likely reflects dopaminergic deficiencies. However, the precise performance profile across time and the pattern of fluctuations within it have not yet been considered, partly due to insufficient methods. Yet, such an analysis may yield important theory-based implications for clinical practice. Thus, in a case-control cross-sectional study, we introduce a new method to investigate performance fluctuations in patients with ADD (n = 76) and ADHD (n = 67) compared to healthy controls (n = 45) in a time estimation task. In addition, we also evaluate the effects of methylphenidate (MPH) treatment on this performance pattern in 29 patients with AD(H)D. Trial-by-trial differences in performance between healthy controls and patients with AD(H)D do not persist continuously over longer time periods. Periods during which no differences in performance between healthy controls and patients occur alternate with periods in which such differences are present. AD(H)D subtype and surprisingly also medication status does not affect this pattern. The presented findings likely reflect (phasic) deficiencies of the dopaminergic system in patients with AD(H)D which are not sufficiently ameliorated by first-line pharmacological treatment. The presented findings carry important clinical and scientific implications.

Substance Use, Resulting Disorders, and Collateral Mental Disorders Among Adolescents in a Special Outpatient Institutions for Addictions Abstract. Objective: Only few clinics offer the outpatient treatment of substance use disorders (SUDs) among adolescents. Therefore, only limited data describe substance use patterns, SUDs, and co-occurring psychiatric disorders characteristic of adolescents who present in such outpatient clinics specialized in the treatment of SUDs. Method: Via interview we collected data from n = 201 patients between 12 and 19 years concerning their substance use, SUDs, and current co-occurring psychiatric disorders. We created descriptive presentation of data regarding use patterns, SUDs, and co-occurring disorders divided by sex and current age. Results: Tobacco (88 %) and cannabis (86 %) were the most frequently used substances. 67 % of all patients presented with more than one SUD, cannabis use disorder being the most prevalent one (84 %). 72 % presented with at least one co-occurring disorder, with conduct disorders (40 %), attention deficit (hyperactivity) disorders (21 %), and depressive disorders (18 %) being the most frequent ones. Conclusions: Adolescent SUD patients often present with co-occurring psychiatric disorders. Institutions for adolescent SUD treatment should also focus on treating co-occurring conduct disorders, depression, and attention deficit disorders.

Tetrahydroisoquinolines (TIQs) such as salsolinol (SAL), norsalsolinol (NSAL) and their methylated derivatives N-methyl-norsalsolinol (NMNSAL) and N-methyl-salsolinol (NMSAL), modulate dopaminergic neurotransmission and metabolism in the central nervous system. Dopaminergic neurotransmission is thought to play an important role in the pathophysiology of chronic tic disorders, such as Tourette syndrome (TS). Therefore, the urinary concentrations of these TIQ derivatives were measured in patients with TS and patients with comorbid attention-deficit/hyperactivity disorder (TS + ADHD) compared with controls. Seventeen patients with TS, 12 with TS and ADHD, and 19 age-matched healthy controls with no medication took part in this study. Free levels of NSAL, NMNSAL, SAL, and NMSAL in urine were measured by a two-phase chromatographic approach. Furthermore, individual TIQ concentrations in TS patients were used in receiver-operating characteristics (ROC) curve analysis to examine the diagnostic value. NSAL concentrations were elevated significantly in TS [434.67 ± 55.4 nmol/l (standard error of mean = S.E.M.), two-way ANOVA, p < 0.0001] and TS + ADHD patients [605.18 ± 170.21 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] compared with controls [107.02 ± 33.18 nmol/l (S.E.M.), two-way ANOVA, p < 0.0001] and NSAL levels in TS + ADHD patients were elevated significantly in comparison with TS patients (two-way ANOVA, p = 0.017). NSAL demonstrated an AUC of 0.93 ± 0.046 (S.E.M) the highest diagnostic value of all metabolites for the diagnosis of TS. Our results suggest a dopaminergic hyperactivity underlying the pathophysiology of TS and ADHD. In addition, NSAL concentrations in urine may be a potential diagnostic biomarker of TS.

Background: Methamphetamine use disorder (MUD) frequently begins in adolescence, often accompanied by other psychiatric or mental disorders. Up to now, no comprehensive review about MUD and comorbid disorders in adolescents is available. We thus aimed to review the literature on comorbid mental disorders and MUD in adolescents in order to identify future research topics. Method : A PubMed search was conducted in July 2019. Relevant comorbidities were defined as attention-deficit disorder with/without hyperactivity, anxiety disorders, depression, eating disorders, post-traumatic stress disorder, psychosis, borderline personality disorder, conduct disorder and antisocial personality disorder, as well as other substance use disorders. For each comorbidity, we summarized prevalence rates, findings on comorbidity mechanisms, and recommended treatment options, if applicable. Results : Few articles focused on MUD in adolescents. Prevalence rates differed largely between comorbid disorders, with tobacco use disorder, conduct disorder, post-traumatic stress disorder, anxiety disorders, and attention-deficit disorders being the most prevalent comorbidities while eating disorders were rare. Examined onset patterns and comorbidity mechanisms indicated three groups of comorbidities: preexisting disorders self-medicated with methamphetamine, disorders induced by chronic methamphetamine use, and disorders arising due to risk factors shared with MUD. Reviewed comorbidities were frequently associated with worse treatment outcomes. Conclusions : The limited evidence is in stark contrast to the presumably high prevalence and relevance of comorbid mental disorders in adolescents with MUD. Suggestions for future research topics, informed by adult findings, include genetic vulnerabilities, biological changes, and consequences of different use patterns. Surprisingly few MUD treatment programs explicitly integrate comorbid mental disorder modules.

Impulsivity and deficits in response inhibition are hallmarks of attention-deficit(-hyperactivity) disorder (AD(H)D), can cause severe problems in daily functioning, and are thus of high clinical relevance. Traditionally, research to elucidate associated neural correlates has intensively, but also quite selectively examined mechanisms during response inhibition in various tasks. Doing so, in-between trial periods or periods prior to the response inhibition process, where no information relevant to inhibitory control is presented, have been neglected. Yet, these periods may nevertheless reveal relevant information. In the present study, using a case-control cross-sectional design, we take a more holistic approach, examining the inter-relation of pre-trial and within-trial periods in a Go/Nogo task with a focus on EEG theta band activity. Applying EEG beamforming methods, we show that the dynamics between pre-trial (pro-active) and within-trial (inhibition-related) control processes significantly differ between AD(H)D subtypes. We show that response inhibition, and differences between AD(H)D subtypes, exhibit distinct patterns of (at least) three factors: (i) strength of pre-trial (pro-active control) theta-band activity, (ii) the inter-relation of pro-active control and inhibition-relation theta band activity and (iii) the functional neuroanatomical region active during theta-related pro-active control processes. This multi-factorial pattern is captured by AD(H)D subtype clinical symptom clusters. The study provides a first hint that novel cognitive-neurophysiological facets of AD(H)D may be relevant to distinguish AD(H)D subtypes., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: The associations of birth order, number of siblings, and ADHD was examined. Method: The analysis based on representative, epidemiological data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study ( N = 13,488). Results: An increased risk for ADHD in firstborn versus youngest born children (odds ratio [OR] = 1.31, 95% confidence interval [CI] [1.09, 1.58]) and also versus children with no sibling (OR = 1.31, 95% CI [1.03, 1.68]) was revealed, while number of siblings was not associated with ADHD. Results remained stable after controlling for confounders. Conclusion: Firstborn children may receive simultaneously less parental resources and more responsibilities if younger siblings are born. This happens during the vulnerable developmental period of ADHD. In addition, due to higher levels of insecurity, parents are assumed to focus more on potential physical or psychological abnormities in their firstborn children. This may result in a diagnostic bias in firstborn children.

Objective: To examine the association of refractive error (myopia, hyperopia, astigmatism) and strabismus with ADHD. Method: Based on data from the large, representative, epidemiological sample of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) study ( N = 13,488), the associations of myopia, hyperopia, astigmatism, and strabismus with ADHD were examined, with and without consideration of other common ADHD risk factors. Results: In single logistic regression models, all examined forms of refractive error and strabismus showed an association with ADHD. After controlling for confounding variables, results remained stable and showed an increased risk for ADHD in children with hyperopia, astigmatism, and strabismus compared with the control group. Only the association between myopia and ADHD in children was not significant. Conclusion: Hyperopia, astigmatism, and strabismus seem to be independently associated with ADHD. Health care professionals in different medical fields should consider this association to adequately diagnose and treat affected children.

Similar to other neurodevelopmental disorders, the diagnosis of attention-deficit hyperactivity disorder (ADHD) is based on clinical and psychosocial assessment. This assessment is performed in clinical practice using the clinical routine interview technique. Domains of the clinical routine interview are, among others, present symptoms, history of present illness and family and developmental history. Family and developmental history are important parts in the diagnostic process of ADHD. In contrast to the domains of present symptoms and history of present illness, there are currently no structured interviews or rating scales available to thoroughly assess family and developmental history in ADHD. The aim of the study was to assess the profile of operationalized data from a structured clinical routine interview addressing family and developmental history from ADHD patients and control participants. A structured interview to assess family and developmental history was derived from the guidelines used at different university hospitals for Child and Adolescent Psychiatry as well as from the descriptions in leading textbooks. Based on these guidelines and descriptions, the interview was an optimization of possible questions. Clinical data were obtained from parents of male patients who had the diagnosis of ADHD between the ages of 12-17 years (n = 44), and of healthy controls (n = 41). Non-metric data were operationalized into three categories, 0-normal behavior, 1-minor pathological behavior, 2-major pathological behavior. ADHD patients express a profile that significantly differs from control participants. Comparison of significant items with the empirical ADHD literature indicates strong agreement. Our findings support the importance and feasibility of the clinical routine interview in family and developmental history in the context of diagnosing ADHD.

ADHD is one of the most prevalent neuropsychiatric disorders of childhood, but symptoms vary considerably between individuals. Therefore, different ADHD subtypes can be distinguished. Yet, it is widely elusive whether the specific subtype is critical to consider when examining treatment effects. Based on theoretical considerations, this could be the case for EEG theta/beta neurofeedback. We examine the effects of such an intervention on rapid response execution and inhibition processes using a Go/Nogo task in the inattentive (ADD) and the combined (ADHD-C) subtype. We show that a single neurofeedback protocol affects opposing deficits depending on the ADHD subtype - namely the execution (in ADD) and inhibition of action (in ADHD-C). No changes occurred in the healthy controls. These findings are discussed in relation to overarching principles of neural oscillations, particularly in the beta frequency band. The data suggest that theta/beta neurofeedback trains a superordinate system strongly related to the function of neural beta frequency oscillations to tune neural networks important for the sampling of sensory information used for behavioral control., (© 2020 The Authors. Developmental Science published by John Wiley & Sons Ltd.)

Objective: Conflict monitoring is well known to be modulated by context. This is known as the Gratton effect, meaning that the degree of interference is smaller when a stimulus-response conflict had been encountered previously. It is unclear to what extent these processes are changed in ADHD. Method: Children with ADHD (combined subtype) and healthy controls performed a modified version of the sequence flanker task. Results: Patients with ADHD made significantly more errors than healthy controls, indicating general performance deficits. However, there were no differences regarding reaction times, indicating an intact Gratton effect in ADHD. These results were supported by Bayesian statistics. Conclusion: The results suggest that the ability to take contextual information into account during conflict monitoring is preserved in patients with ADHD despite this disorder being associated with changes in executive control functions overall. These findings are discussed in light of different theoretical accounts on contextual modulations of conflict monitoring.

About 50% of attention deficit hyperactivity disorder (ADHD) patients suffer from comorbidity with oppositional defiant disorder/conduct disorder (ODD/CD). Most previous studies on structural morphology did not differentiate between pure (ADHD-only) and comorbid ADHD (ADHD+ODD/CD). Therefore, we aimed to investigate the structural profile of ADHD-only versus ADHD+ODD/CD spanning the indices subcortical and cortical volume, cortical thickness, and surface area. We predicted a reduced total gray matter, striatal, and cerebellar volume in both patient groups and a reduced amygdalar and hippocampal volume for ADHD+ODD/CD. We also explored alterations in prefrontal volume, thickness, and surface area. We acquired structural images from an adolescent sample ranging from 11 to 17 years, matched with regard to age, pubertal status, and IQ-including 36 boys with ADHD-only, 26 boys with ADHD+ODD/CD, and 30 typically developing (TD) boys. We analyzed structural data with FreeSurfer. We found reductions in total gray matter and total surface area for both patient groups. Boys with ADHD+ODD/CD had a thicker cortex than the other groups in a right rostral middle frontal cluster, which was related to stronger ODD/CD symptoms, even when controlling for ADHD symptoms. No group differences in local cortical volume or surface area emerged. We demonstrate the necessity to carefully differentiate between ADHD and ADHD+ODD/CD. The increased rostral middle frontal thickness might hint at a delayed adolescent cortical thinning in ADHD+ODD/CD. Patients with the double burden ADHD and ODD or CD seem to be even more affected than patients with pure ADHD., (© 2019 The Authors. Human Brain Mapping published by Wiley Periodicals, Inc.)

Background: Various lines of research suggest that the stability of neural processes is low in attention-deficit/hyperactivity disorder (ADHD). Considering overarching neural principles, this lack of stability relates to increased levels of neural noise. However, no study has directly examined neural noise in ADHD. Likewise, it is unknown whether the modulation of neural noise reflects a mechanistic link as to why methylphenidate (MPH) is effective in treating impulsivity in ADHD., Methods: We compared neural noise between 29 juvenile patients with ADHD and 32 healthy control subjects and examined the effects of MPH. We examined 1/f neural noise of electroencephalogram data collected while participants performed a response inhibition (Go/NoGo) task., Results: Specific during NoGo trials, children with ADHD showed more neural noise than healthy control subjects. This was especially the case with regard to the theta frequency band, which is very closely related to cognitive control. MPH treatment reduced neural noise in ADHD to the level of healthy control subjects. Correlational analyses showed a direct relationship between decreases in neural noise and increases in behavioral performance. Mechanistically, this can be explained by the MPH-induced increase in dopaminergic neurotransmission that enhances the signal-to-noise ratio in neural networks and thus reduces neural noise., Conclusions: This study is the first to demonstrate increased (pink) neural noise in patients with ADHD and its reduction through MPH treatment. The study reveals an important mechanistic link as to why MPH is effective in treating impulsivity in ADHD., (Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: The purpose of the present study was the analysis of the association between consumption of candy and fruit gums, diagnosis of attention deficit hyperactivity disorder (ADHD), and behavioural problems. Methods: In total, 1,187 children and adolescents of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS) were analyzed. Results: It was observed that children and adolescents with ADHD as compared to healthy controls (HC) reported to consume more frequently and higher amounts of candy and fruit gums and that hyperactivity was associated with frequent candy and fruit gum consumption. Conclusions: Because with the present design no conclusions on causality or directionality of the found associations could be drawn, results are discussed quite broadly in the light of several previously published interpretations, also to serve as a generator for further research. One more innovative speculation is that children and adolescents with ADHD may consume more frequently candy and fruit gums in order i) to compensate for their higher needs of energy resulting from hyperactive behaviour and/or ii) to compensate for the ADHD-typical deficits in the "reward cascade".

Inhibitory control deficits are a hallmark in ADHD. Yet, inhibitory control includes a multitude of entities (e.g. 'inhibition of interferences' and 'action inhibition'). Examining the interplay between these kinds of inhibitory control provides insights into the architecture of inhibitory control in ADHD. Combining a Simon task and a Go/Nogo task, we assessed the interplay of 'inhibition of interferences' and 'action inhibition'. This was combined with EEG recordings, EEG data decomposition and source localization. Simon interference effects in Go trials were larger in ADHD. At the neurophysiological level, this insufficient inhibition of interferences in ADHD related to the superior parietal cortex. Simon interference effects were absent in action inhibition (Nogo) trials in ADHD, compared to controls. This was supported by bayesian statistics. The power of effects was higher than 95%. The differential effects between the groups were associated with modulations of neurophysiological response selection processes in the superior frontal gyrus. ADHD is not only associated with deficits in inhibitory control. Rather, the organization and architecture of the inhibitory control system is different in ADHD. Distinguishable inhibitory control processes operate on a hierarchical 'first come, first serve' basis and are not integrated in ADHD. This is a new facet of ADHD., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Patients with attention deficit hyperactivity disorder (ADHD) suffer from poor emotion regulation that might arise from problems in the distribution of attentional resources when confronted with emotional distractors. Previous studies investigating the neurocognitive basis of these problems remain inconclusive. Moreover, most of these studies did not exclude participants with comorbidity, particularly of conduct or oppositional defiant disorder. The aim of this study was to assess alterations in fronto-limbic activation in ADHD adolescents specifically during negative distractors in an emotional attention task. For this purpose, we used functional magnetic resonance imaging to assess 25 boys with noncomorbid ADHD and 25 typically developing (TD) boys while they performed an emotional attention task with positive, negative, and neutral emotional distractors. Boys with ADHD had increased activation relative to TD boys specifically during the negative valenced stimuli in an emotional processing network comprising left anterior insula reaching into the inferior frontal gyrus. The findings suggest altered salience processing in ADHD of negative valenced emotional stimuli that may lead to higher distractibility in ADHD specifically when faced with negative emotional distractors., (© 2018 Wiley Periodicals, Inc.)

Even though deficits in inhibitory control and conflict monitoring are well-known in ADHD, factors that further modulate these functions remain to be elucidated. One factor that may be of considerable importance is how inhibitory control is modulated by multisensory information processing. We examined the influence of concurrent auditory conflicting or redundant information on visually triggered response inhibition processes in adolescent ADHD patients and healthy controls. We combined high-density event-related potential (ERP) recordings with source localization to delineate the functional neuroanatomical basis of the involved neurophysiological processes. In comparison to controls, response inhibition (RI) processes in ADHD were compromised in conflicting conditions, but showed no differences to controls when redundant or no concurrent auditory information was presented. These effects were reflected by modulations at the response selection stage (P3 ERP) in the medial frontal gyrus (BA32), but not at the attentional selection (P1, N1 ERPs) or resource allocation level (P2 ERP). Conflicting information during RI exerts its influences in adolescent ADHD via response selection mechanisms, but not via attentional selection. It is not the mere presence of concurrent information, but the presence of conflicting information during RI that may destabilize goal shielding processes in medial frontal cortical regions, by means of increasing the automaticity of response tendencies. The occurring RI deficits might relate to the increased impulsivity in adolescent ADHD and a corresponding vulnerability to react to an increased automaticity of pre-potent response tendencies. ADHD patients show a bias to a specific content of information which can modulate inhibitory control.

Attention Deficit Hyperactivity Disorder (ADHD) is a disorder affecting cognitive control. These functions are important to achieve goals when different actions need to be executed in close succession. This type of multi-component behavior, which often further requires the processing of information from different modalities, is important for everyday activities. Yet, possible changes in neurophysiological mechanisms have not been investigated in adolescent ADHD. We examined N = 31 adolescent ADHD patients and N = 35 healthy controls (HC) in two Stop-Change experiments using either uni-modal or bi-modal stimuli to trigger stop and change processes. These stimuli were either presented together (SCD0) or in close succession of 300 milliseconds (SCD300). Using event-related potentials (ERP), EEG data decomposition and source localization we analyzed neural processes and functional neuroanatomical correlates of multicomponent behavior. Compared to HCs, ADHD patients had longer reaction times and higher error rates when Stop and Change stimuli were presented in close succession (SCD300), but not when presented together (SCD0). This effect was evident in the uni-modal and bi-modal experiment and is reflected by neurophysiological processes reflecting response selection mechanisms in the inferior parietal cortex (BA40). These processes were only detectable after accounting for intra-individual variability in neurophysiological data; i.e. there were no effects in standard ERPs. Multi-component behavior is not always deficient in ADHD. Rather, modulations in multi-component behavior depend on a critical temporal integration window during response selection which is associated with functioning of the inferior parietal cortex. This window is smaller than in HCs and independent of the complexity of sensory input.

It is far from conclusive what distinguishes the inattentive (ADD) and the combined (ADHD-C) subtype of ADHD on the neuronal level. Theoretical considerations suggest that especially interval timing processes may dissociate these subtypes from each other. Combining high-density EEG recordings with source localization analyses, we examine whether there are ADHD-subtype specific modulations of neurophysiological processes subserving interval timing in matched groups of ADD (n = 16), ADHD-C (n = 16) and controls (n = 16). Patients with ADD and ADHD-C show deficits in interval timing, which was correlated with the degree of inattention in ADD patients. Compared to healthy controls, patients with ADHD-C display a somewhat weaker, yet consistent response preparation process (contingent negative variation, CNV). In patients with ADD, the early CNV is interrupted, indicating an oscillatory disruption of the interval timing process. This is associated with activations in the supplemental motor areas and the middle frontal gyrus. Patients with ADD display adequate feedback learning mechanisms (feedback-related negativity, FRN), which is not the case in patients with ADHD-C. The results suggest that altered pacemaker-accumulation processes in medial frontal structures distinguish the ADD from the ADHD-C subtype. Particularly in patients with ADD phasic interruptions of preparatory neurophysiological processes are evident, making this a possible diagnostic feature.

In Attention Deficit Hyperactivity Disorder (AD(H)D), treatments using methylphenidate (MPH) and behavioral interventions like neurofeedback (NF) reflect major therapeutic options. These treatments also ameliorate executive dysfunctions in AD(H)D. However, the mechanisms underlying effects of MPH and NF on executive functions in AD(H)D (e.g. the ability to inhibit prepotent responses) are far from understood. It is particularly unclear whether these interventions affect similar or dissociable neural mechanisms and associated functional neuroanatomical structures. This, however, is important when aiming to further improve these treatments. We compared the neurophysiological mechanisms of MPH and theta/beta NF treatments on inhibitory control on the basis of EEG recordings and source localization analyses. The data show that MPH and theta/beta NF both increase the ability to inhibit pre-potent responses to a similar extent. However, the data suggest that MPH and NF target different neurophysiological mechanisms, especially when it comes to functional neuroanatomical structures associated with these effects. Both treatments seem to affect neurophysiological correlates of a 'braking function' in medial frontal areas. However, in case of the NF intervention, inferior parietal areas are also involved. This likely reflects the updating and stabilisation of efficient internal representations in order to initiate appropriate actions. No effects were seen in correlates of perceptual and attentional selection processes. Notably, reliable effects were only obtained after accounting for intra-individual variability in the neurophysiological data, which may also explain the diversity of findings in studies on treatment effects in AD(H)D, especially concerning neurofeedback., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Attention Deficit / Hyperactivity Disorder (ADHD) and Chronic Tic Disorder (CTD) are two common and frequently co-existing disorders, probably following an additive model. But this is not yet clear for the basic sensory function of colour processing sensitive to dopaminergic functioning in the retina and higher cognitive functions like attention and interference control. The latter two reflect important aspects for psychoeducation and behavioural treatment approaches., Methods: Colour discrimination using the Farnsworth-Munsell 100-hue Test, sustained attention during the Frankfurt Attention Inventory (FAIR), and interference liability during Colour- and Counting-Stroop-Tests were assessed to further clarify the cognitive profile of the co-existence of ADHD and CTD. Altogether 69 children were classified into four groups: ADHD (N = 14), CTD (N = 20), ADHD+CTD (N = 20) and healthy Controls (N = 15) and compared in cognitive functioning in a 2×2-factorial statistical model., Results: Difficulties with colour discrimination were associated with both ADHD and CTD factors following an additive model, but in ADHD these difficulties tended to be more pronounced on the blue-yellow axis. Attention problems were characteristic for ADHD but not CTD. Interference load was significant in both Colour- and Counting-Stroop-Tests and unrelated to colour discrimination. Compared to Controls, interference load in the Colour-Stroop was higher in pure ADHD and in pure CTD, but not in ADHD+CTD, following a sub-additive model. In contrast, interference load in the Counting-Stroop did not reveal ADHD or CTD effects., Conclusion: The co-existence of ADHD and CTD is characterized by additive as well as sub-additive performance impairments, suggesting that their co-existence may show simple additive characteristics of both disorders or a more complex interaction, depending on demand. The equivocal findings on interference control may indicate limited validity of the Stroop-Paradigm for clinical assessments.

There are large overlaps in cognitive deficits occurring in attention deficit disorder (ADD) and neurodevelopmental disorders like neurofibromatosis type 1 (NF1). This overlap is mostly based on clinical measures and not on in-depth analyses of neuronal mechanisms. However, the consideration of such neuronal underpinnings is crucial when aiming to integrate measures that can lead to a better understanding of the underlying mechanisms. Inhibitory control deficits, for example, are a hallmark in ADD, but it is unclear how far there are similar deficits in NF1. We thus compared adolescent ADD and NF1 patients to healthy controls in a Go/Nogo task using behavioural and neurophysiological measures. Clinical measures of ADD-symptoms were not different between ADD and NF1. Only patients with ADD showed increased Nogo errors and reductions in components reflecting response inhibition (i.e. Nogo-P3). Early perceptual processes (P1) were changed in ADD and NF1. Clinically, patients with ADD and NF1 thus show strong similarities. This is not the case in regard to underlying cognitive control processes. This shows that in-depth analyses of neurophysiological processes are needed to determine whether the overlap between ADD and NF1 is as strong as assumed and to develop appropriate treatment strategies.

Pre- and perinatal complications have been implicated in the onset and clinical expression of Tourette syndrome albeit with considerable inconsistencies across studies. Also, little is known about their role in co-occurring obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD) in individuals with a tic disorder. Therefore, we aimed to investigate the role of pre- and perinatal complications in relation to the presence and symptom severity of chronic tic disorder and co-occurring OCD and ADHD using data of 1113 participants from the Tourette International Collaborative Genetics study. This study included 586 participants with a chronic tic disorder and 527 unaffected family controls. We controlled for age and sex differences by creating propensity score matched subsamples for both case-control and within-case analyses. We found that premature birth (OR = 1.72) and morning sickness requiring medical attention (OR = 2.57) were associated with the presence of a chronic tic disorder. Also, the total number of pre- and perinatal complications was higher in those with a tic disorder (OR = 1.07). Furthermore, neonatal complications were related to the presence (OR = 1.46) and severity (b = 2.27) of co-occurring OCD and also to ADHD severity (b = 1.09). Delivery complications were only related to co-occurring OCD (OR = 1.49). We conclude that early exposure to adverse situations during pregnancy is related to the presence of chronic tic disorders. Exposure at a later stage, at birth or during the first weeks of life, appears to be associated with co-occurring OCD and ADHD., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Neurofeedback is increasingly recognized as an intervention to treat core symptoms of attention deficit hyperactivity disorder (ADHD). Despite the large number of studies having been carried out to evaluate its effectiveness, it is widely elusive what neuronal mechanisms related to the core symptoms of ADHD are modulated by neurofeedback. 19 children with ADHD undergoing 8 weeks of theta/beta neurofeedback and 17 waiting list controls performed a Go/Nogo task in a pre-post design. We used neurophysiological measures combining high-density EEG recording with source localization analyses using sLORETA. Compared to the waiting list ADHD control group, impulsive behaviour measured was reduced after neurofeedback treatment. The effects of neurofeedback were very specific for situations requiring inhibitory control over responses. The neurophysiological data shows that processes of perceptual gating, attentional selection and resource allocation processes were not affected by neurofeedback. Rather, neurofeedback effects seem to be based on the modulation of response inhibition processes in medial frontal cortices. The study shows that specific neuronal mechanisms underlying impulsivity are modulated by theta/beta neurofeedback in ADHD. The applied neurofeedback protocol could be particularly suitable to address inhibitory control. The study validates assumed functional neuroanatomical target regions of an established neurofeedback protocol on a neurophysiological level.

Objective: This study aims to ascertain once and for all whether children and adolescents affected by ADHD show a higher risk for accidents, as well as investigating a possible association between the administration of ADHD-specific medication and the occurrence of accidents., Method: Two exceptionally large sets of data were implemented in this analysis. Participants included children and adolescents representative of the entire German population. Data for Survey 1 was collected through extensive administration of questionnaires. Data for Survey 2 stemmed from the records of a leading German health insurance company. In terms of statistical analysis, chi-square tests as well as logistic regression analyses were applied and odds ratios (ORs) were determined., Results: Innovative results are presented showing a significantly higher likelihood for ADHD-affected youngsters to be involved in accidents compared with their nonaffected counterparts (Survey 1: OR = 1.60; Survey 2: OR = 1.89) but lacking an overall significant influence of medication regarding the occurrence of accidents (Survey 1: OR = 1.28; Survey 2: OR = 0.97). Frequency of accidents could be predicted by ADHD, gender, and age in both samples. Medication intake served as a weak predictor only in Survey 2., Conclusion: It has been determined in two representative and independent German samples that youngsters with ADHD are at a significantly higher risk of being involved in accidents. In the future, this should always be considered when setting up a treatment plan to ensure a safer and healthier coming of age without relying solely on specific effects of medication. (J. of Att. Dis. 2016; 20(6) 501-509)., (© The Author(s) 2014.)

Objective: The study examines the role of obsessive-compulsive symptoms (OCS) as a part of the psychopathology of children with chronic tic disorders (CTD) and/or attention-deficit hyperactivity disorder (ADHD)., Method: We assessed the psychopathology of four large patient groups without further psychiatric disorders: CTD (n = 112), CTD + ADHD (n = 82), ADHD (n = 129), and controls (n = 144)) by implementing the Child Behavior Checklist (CBCL). We compared the main effects for CTD and ADHD with and without including OCS as covariates., Results: Including OCS led to substantially different main effects for CTD on seven out of eight CBCL subscales. Slightly different main effects for ADHD were determined with respect to ADHD, mainly on the subscale withdrawn., Conclusions: OCS are closely related to CTD-associated psychopathology and - to a lesser extent, but nevertheless of importance in daily clinical practice - on ADHD-related symptoms. This information can be helpful in implementing more precise diagnostics and treatment in daily routine care.

Attention deficit hyperactivity disorder is one of the most frequent neuropsychiatric disorders in childhood. Transcranial magnetic stimulation studies based on muscle responses (motor-evoked potentials) suggested that reduced motor inhibition contributes to hyperactivity, a core symptom of the disease. Here we employed the N100 component of the electroencephalographic response to transcranial magnetic stimulation as a novel marker for a direct assessment of cortical inhibitory processes, which has not been examined in attention deficit hyperactivity disorder so far. We further investigated to what extent affected children were able to regulate motor cortical inhibition, and whether effects of age on the electroencephalographic response to transcranial magnetic stimulation were compatible with either a delay in brain maturation or a qualitatively different development. N100 amplitude evoked by transcranial magnetic stimulation and its age-dependent development were assessed in 20 children with attention deficit hyperactivity disorder and 19 healthy control children (8-14 years) by 64-channel electroencephalography. Amplitude and latency of the N100 component were compared at rest, during response preparation in a forewarned motor reaction time task and during movement execution. The amplitude of the N100 component at rest was significantly lower and its latency tended to be shorter in children with attention deficit hyperactivity disorder. Only in controls, N100 amplitude to transcranial magnetic stimulation was reduced by response preparation. During movement execution, N100 amplitude decreased while motor evoked potential amplitudes showed facilitation, indicating that the electroencephalographic response to transcranial magnetic stimulation provides further information on cortical excitability independent of motor evoked potential amplitudes and spinal influences. Children with attention deficit hyperactivity disorder showed a smaller N100 amplitude reduction during movement execution compared with control children. The N100 amplitude evoked by transcranial magnetic stimulation decreased with increasing age in both groups. The N100 reduction in children with attention deficit hyperactivity disorder at all ages suggests a qualitative difference rather than delayed development of cortical inhibition in this disease. Findings further suggest that top-down control of motor cortical inhibition is reduced in children with attention deficit hyperactivity disorder. We conclude that evoked potentials in response to transcranial magnetic stimulation are a promising new marker of cortical inhibition in attention deficit hyperactivity disorder during childhood.

Although ADHD significantly affects the quality of life (QoL) of patients and their families, QoL in children with ADHD has rarely been investigated in association with psychopathological profile, and the relationship remains unclear. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL(®), a modified-release methylphenidate, in routine care of children and adolescents (aged 6-17 years) with ADHD. At baseline, questionnaires assessing psychopathological profile (Strengths and Difficulties Questionnaire, SDQ; parental ratings) and QoL (KINDL; parent, child or adolescent versions) were completed; QoL was reassessed at final visit. We analysed the relationship between psychopathology and parent/patient-rated QoL in ADHD at baseline. Data from 721 consecutively referred children and adolescents were analysed. QoL was similarly low from parent and self-ratings and independent of severity on the SDQ subscale hyperactivity/inattention. Self-ratings indicated that additional conduct disorder was associated with further reduction in QoL. Similarly, children with high scores from parent and adolescent ratings on the SDQ subscale conduct problems had reduced QoL on some KINDL subscales. Adolescents with ADHD not receiving medication at baseline reported lower QoL than those already on medication. Results show that children and adolescents with ADHD have low QoL, independent of core symptom severity. Additional conduct problems may further impact QoL negatively, while ADHD medication use may show a trend towards improved QoL. Not all psychopathological problems associated with ADHD affect QoL similarly. As parents appear to have a less critical view of QoL compared with children's self-ratings, both parent and child ratings should be included in clinical assessments.

Background: We aimed to investigate the influences of attention deficit/hyperactivity disorder (ADHD) on response evaluation, as reflected by the postimperative negative variation (PINV), a slow event-related potential., Methods: We investigated PINV as an indicator of performance uncertainty in an audio-visual contingent negative variation (CNV) paradigm with an interstimulus interval of 3 seconds. A constant, unilateral, quick motor reaction with either the right or the left thumb was required after an auditory forewarned (S1) visual imperative stimulus (S2). We examined 18 ADHD patients (combined or hyperactive-impulsive subtype) aged between 8 and 14 years and an age-, sex and IQ-matched control group of 19 healthy subjects using 64-channel high-density EEG. A first run was recorded drug-free, a second one under methylphenidate (MPH) medication in the ADHD group., Results: We found a significantly increased negativity of the PINV-component over the ventrolateral prefrontal cortex in ADHD children compared to the healthy control group. PINV amplitude was influenced by movement side, most likely due to the slightly more difficult task when left hand responses were required. After the intake of MPH, PINV amplitudes of ADHD children normalized., Conclusions: We conclude that children with ADHD are likely to be more uncertain about the correctness of their performance and interpret the increased PINV as a hint towards compensatory mechanisms for a deficit in the evaluation of contingencies. Further studies are needed to assess the exact extent to which remainders of eye-movement related potentials contribute to PINV amplitude despite the correction for eye-artifacts.

The aim of the present study was to investigate the effect of both tic disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) on attentional functions. N=96 children and adolescents participated in the study, including n=21 subjects with TD, n=23 subjects with ADHD, n=25 subjects with TD+ADHD, and n=27 controls. Attentional performance was tested based on four computerized attention tasks (sustained attention, divided attention, go/nogo and set shifting). The effect of TD as well as ADHD on attentional performance was tested using a 2 × 2 factorial approach. A diagnosis of TD had no negative impact on attentional functions but was associated with improved performance in the set shifting task. By contrast, regardless of a diagnosis of TD, subjects with ADHD were found to perform worse in the sustained attention, divided attention and go/nogo task. No interaction effect between the factors TD and ADHD was revealed for any of the attention measures. Our results add to findings from other areas of research, showing that in subjects with TD and ADHD, ADHD psychopathology is often the main source of impairment, whereas a diagnosis of TD has little or no impact on neuropsychological performance in most cases and even seems to be associated with adaptive mechanisms.

In developmental psychopathology, differentiating between the coexistence and the clinical entity of two problem areas is of utmost importance. So far, logistic regression analysis has already provided helpful answers, as shown in studies on comorbidity of tic disorders. While the concept of bridging symptoms may be investigated adequately by both logistic regression and the network approach, the former (latent variable) seems to be of advantage with regard to the problems of multiple comorbidities and development.

Although stimulants as the treatment of choice are widely prescribed in ADHD, little is known about their long-term neurobiological effects. Hence, for the first time the present study examined the long-term effects of chronic methylphenidate (MPH) administration on striatal 5-hydroxytryptamine transporter (5-HTT) densities in an animal model of ADHD. First, it compared the normal development of striatal 5-HTT densities of spontaneously hypertensive rats (SHR) as an animal model of ADHD and Wistar Kyoto (WKY) rats as controls; binding of the highly selective ligand of 5-HTT [(3)H]paroxetine was determined on membrane preparations of the striatum of SHR and WKY rats on postnatal days 25, 50, and 90, i.e. from the time of weaning until adulthood. Second, the long-term effect of chronic administration of 2 mg/kg per day MPH at two different developmental stages (days 25-39 or 50-64) on the striatal 5-HTT density was examined in both rat strains at day 90. Long-term effects of MPH treatment on striatal 5-HTT density in adulthood could be ruled out in both healthy (WKY) and "ADHD" rats (SHR). But a higher striatal 5-HTT density in older SHR versus WKY rats might indicate ADHD specific changes in the 5-HT system that needs further investigation not only in animals.

Introduction: This study aims to assess cross-cultural similarities and differences in broadband psychopathology in two naturalistic clinical samples of children diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) combined type according to DSM-IV criteria or with Hyperkinetic Disorder (HD) according to ICD-10 criteria., Methods: We compared two clinical samples of children with ADHD combined type (Brazil, N=248) and HD (Germany; N=154) to controls (Brazil N=71; Germany N=135) using the Child Behavior Checklist (CBCL). ROC-curves (Receiver Operating Characteristic) were determined to evaluate the discriminating validity of the CBCL Attention Problem scale. A two-factorial ANOVA was computed across all 8 scales of the CBCL., Results: Although Brazilian parents reported significantly higher scores on all CBCL scales than German parents (P<0.05), a similar CBCL profile was detected in both cultures., Conclusion: Despite the use of different diagnostic systems (DSM-IV vs. ICD-10) and the presence of other clinical differences, the similar broadband psychopathological profile of the CBCL in the two samples provides evidence that dimensional symptoms associated with the categorical diagnosis of ADHD combined type might be comparable in two clinical settings with diverse cultural background.

In daily clinical practice of child psychiatry tic disorders (TD) and attention-deficit/hyperactivity disorder (ADHD) as well as their co-existence are common and need careful evidence-based approaches in differential diagnostics and treatment choice. Hence, their relationship at different levels (e.g., psychopathology, neuropsychology, neurobiology, treatment) needs to be elucidated in more detail. The articles of this supplement deal with this subject. It is unclear if TD + ADHD represents an own clinical entity and which component (TD vs. ADHD) is most important in case of co-existence with respect to accompanying problems like emotional or cognitive disturbances. This editorial gives a short overview of the essential research topics concerning TD + ADHD and shows where (in this ECAP supplement and other literature) empirically based answers can be found. Probably, the identification of separate or common "endophenotypes" for TD-only, ADHD-only and for TD + ADHD would help to sort out the complexities and this supplement may nurture such a perspective of future research for a better understanding and treatment of youths with TD + ADHD and their families.

Background: In Tourette syndrome (TS) as a neurodevelopmental disorder not only the tics but also the comorbid conditions change with increasing age. ADHD is highly comorbid with TS and usually impairs psychosocial functioning more than the tics. Its impact on further comorbidity during development is important for clinical practice and still a matter of debate., Method: Aspects of developmental psychopathology considering the impact of ADHD were examined by logistic regression (year wisely) in a cross-sectional sample of children and adolescents (n = 5060) from the TIC database., Results: In TS+ADHD (compared to TS-ADHD) higher rates of comorbid conditions like OCD, anxiety disorders, CD/ODD and mood disorders were found in children (5-10 years). In adolescents (11-17 years) higher comorbidity rates in TS+ADHD remained only for CD/ODD and mood disorders. Accordingly, for OCD and anxiety disorders there was a steeper year wise increase of these comorbidities in TS-ADHD while it was a similar for CD/ODD and mood disorders in TS-ADHD as well as TS+ADHD., Conclusion: Children with TS+ADHD have more comorbidities than the TS-ADHD group, whereas in both adolescent groups this did no longer hold for OCD and anxiety disorders. These findings indicate that in TS comorbid ADHD is associated with high rates of externalizing and internalizing problems, whereas TS without ADHD is associated only with internalizing problems in adolescence.

Background: The causes and pathophysiological mechanisms of the common comorbidity of tic disorders and Attention-deficit/Hyperactivity disorder (TD + ADHD; about 50% of TD, about 20% of ADHD) still remain unclear. Studies with a 2 x 2 design comparing groups of children with TD, ADHD, TD + ADHD and healthy controls are in need and may disentangle the influences of TD versus ADHD in the case of comorbidity. Unfortunately, conceptual and methodological problems can restrain possible conclusions from these studies., Method: A review of the literature on artifactual and non-artifactual models of comorbidity in general and specially for TD + ADHD was conducted., Results: The first section describes various possible models of comorbidity and their corresponding hypotheses concerning expected patterns of findings comparing groups of children with TD, ADHD, TD + ADHD and healthy controls. In the second part research results concerning psychopathological, neuropsychological, neurophysiological, structural and functional imaging, as well as genetic characteristics are summarized. In the third section possible conclusions and their limitations due to conceptual and methodological problems possibly contributing to the ambiguous results are discussed. Finally, future research strategies and the need for full causal models are outlined., Conclusion: Some components of the etiological pathways of TD + ADHD may well be shared with the 'pure' conditions while others may be unique.

Objective: In Chronic Tic Disorders (CTD) associated Attention Deficit Hyperactivity Disorder (ADHD) is very common. Hence, it is important to clarify how both conditions are related to cognitive dysfunctions in patients with CTD+ADHD comorbidity. Recent studies on neuropsychology revealed equivocal results, mostly due to methodological shortcomings like problems in sample composition. Thus better and more detailed information on this topic is needed to improve diagnostic and treatment approaches., Method: Three tasks related to different domains of executive functions (the Matching Familiar Figures Test, the Stroop color-word interference task, and a computerized version of the Wisconsin Card Sorting Test) have been performed in two independent samples (altogether n = 138 children) both including four groups of children (CTD-only, CTD+ADHD, ADHD-only, healthy controls) matched for age and IQ. To specify the influence of either tics or ADHD-symptoms on executive functions and to answer the question of their interactive or additive relationship two-way analyses of variance (MANOVA) for the factors CTD (yes,-no) x ADHD (yes,no) were conducted. Eta squared was calculated to reveal the effect sizes for each factor. For a deeper understanding of group differences and to better enable the comparison with data in literature, additional analyses of variance (ANOVA) with posthoc testing were applied., Results: In summary, there was a main effect only for the factor ADHD reflected by decreased performance, while no main effect of the factor CTD could be found. Admittedly, the effects were not uniform in both samples. However, in all three tasks and both samples, uniformly no interaction between the main factors has been observed., Conclusions: In cases of coexisting CTD+ADHD the factor ADHD shows the main negative impact on neuropsychological performance and this impact seems to be independent of any feature of the coexisting tics (additive model). This supports the notion to primarily treat the ADHD-symptoms in order to increase cognitive self regulatory abilities of these children. Contrarily, tics seem to have little impact on cognitive performance in most cases.

The nature of the co-occurrence of chronic tic disorders (CTD) and attention deficit hyperactivity disorder (ADHD) is unclear. Especially in the field of psychopathology, the relationship of CTD and ADHD remains to be clarified. Thus, the aim of the present chart review study was to specify the contribution of CTD and/or ADHD to the psychopathological profile of the comorbid group (CTD+ADHD). The psychopathological profiles of four large groups (CTD-only (n=112), CTD+ADHD (n=82), ADHD-only (n=129), controls (n=144)) were measured by the eight subscales of the Child Behavior Checklist (CBCL) and analyzed by a 2x2 factorial design followed by contrasts. There were main effects of ADHD diagnosis on all but one subscale of the CBCL (Somatic Complaints). For CTD diagnosis, main effects were found for Attention Problems, Anxious/Depressed, Thought Problems, Social Problems and Somatic Complaints. The only interaction effect was seen for Somatic Complaints. While CTD and ADHD were both related to internalizing psychopathology of children in the CTD+ADHD group, ADHD had the largest effect on externalizing psychopathology in the comorbid group. At the level of psychopathology, an additive model for the co-occurrence of CTD and ADHD is strongly supported. In the comorbid group (CTD+ADHD), the ADHD diagnosis shows the strongest relation to externalizing psychopathology.